Salem Y. Mohamed

Lactobacillus reuteri in management of Helicobacter pylori infection in dyspeptic patients: a double-blind placebo-controlled randomized clinical trial

Introduction: The eradication rate of Helicobacter pylori following the standard triple therapy is declining. This study was conducted to test whether the addition of Lactobacillus reuteri to the standard triple therapy improves the eradication rates as well as the clinical and pathological aspects in H. pylori infection. Methods: A total of 70 treatment-naïve patients were randomly assigned into group A (the L. reuteri treated group) and group B (the placebo control group). Patients were treated by the standard triple therapy for 2 weeks and either L. reuteri or placebo for 4 weeks. They were examined by symptom questionnaire, H. pylori antigen in stool, upper endoscopy with biopsies for rapid urease test and histopathological examination before treatment and 4 weeks after treatment. Results: The eradication rate of H. pylori infection was 74.3% and 65.7% for both L. reuteri and placebo treated groups, respectively. There was a significant difference regarding the reported side effects, where patients treated with L. reuteri reported less diarrhea and taste disorders than placebo group. A significant difference within each group was observed after treatment regarding Gastrointestinal Symptom Rating Scale (GSRS) scores; patients treated with L. reuteri showed more improvement of gastrointestinal symptoms than the placebo treated group. The severity and activity of H. pylori associated gastritis were reduced after 4 weeks of therapy in both groups. The L. reuteri treated group showed significant improvement compared with the placebo treated group. Conclusion: Triple therapy of H. pylori supplemented with L. reuteri increased eradication rate by 8.6%, improved the GSRS score, reduced the reported side effects and improved the histological features of H. pylori infection when compared with placebo-supplemented triple therapy.

Prognostic significance of the genetic and the immunohistochemical expression of epithelial-mesenchymal-related markers in colon cancer

BACKGROUND Epithelial-mesenchymal transition (EMT) is one of the main events in colorectal cancer (CRC) spread. Snail-1 is a zinc transcription factor that mediates EMT in tumor cells probably by down-regulation of E-cadherin and claudin-1. OBJECTIVES To detect the expression of epithelial markers (claudin-1 and E-cadherin) and mesenchymal markers (snail-1 and vimentin) in primary cancer colon. Also, to select stage II cancer patients of a high risk that can benefit from postoperative adjuvant chemotherapy. METHODS Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical analysis were performed to investigate snail-1, claudin-1, E-cadherin and vimentin expressions at mRNA and protein levels in fresh tissues of cancer colon and normal colonic mucosa. The correlations between the expression of these markers and clinicopathological parameters were performed. RESULTS Normal colonic mucosa revealed complete membranous expression of claudin-1, preserved E-cadherin and negative snail-1 and vimentin expressions. Compared to control, the expression of snail-1 and vimentin mRNA in cancer colon was significantly up-regulated while the expression of claudin-1 and E-cadherin mRNA was significantly down-regulated. These changes were significantly associated with stage and lymph node involvement at both mRNA and protein levels (p< 0.05). There were significant negative correlations between vimentin and each of E-cadherin and claudin-1 gene expression and between snail-1 and each of E-cadherin and claudin-1 gene expression. Moreover, these changes were independent predictors of recurrence of stage II cancer colon cases. CONCLUSION There is a clinical significance of snail-1, claudin-1, E-cadherin and vimentin as possible markers for recognizing patients with lymph node involvement, advanced stage and high incidence of tumor recurrence in cancer colon.

Prognostic Value of Cyclin D1 and CD44 Expression in Gastric Adenocarcinoma

BackgroundWorldwide, gastric carcinoma (GC) is the 5th most common malignancies in both sexes representing 6.8% of the total fatalities and is the 3rd leading cause of cancer death representing 8.8% of total fatalities. In Egypt, GC considers the 12th leading cause of cancer death representing 2.2% of the total cancer mortality. A growing body of evidence supports that cancer stem cells (CSCs) are resistant to chemotherapy or radiation, and the cell adhesion molecule CD44 has been identified as a cell surface marker associated with cancer stem cell in several types of tumors including gastric cancer. CD44 regulates gastric stem cell proliferation by increasing cyclin D1 expression which represents an important regulatory protein in the cell cycle transition from G1 phase to S phase. This study aimed to investigate whether cyclin D1 and CD44 can be used as prognostic indicators in gastric cancer.Material and MethodsForty formalin-fixed and paraffin-embedded gastric tissues, obtained from patients who underwent endoscopic resection or surgical resection, constituted the group of our study. The immunohistochemical expression of cyclin D1 and CD44 was examined and correlated with clinical-pathological parameters and outcome of the patients.ResultsOverexpression of CD44 and cyclin D1 was noted (in of 55 and 50% respectively). Cyclin D1 and CD44 positive expressions in GC were positively correlated with tumor differentiation (p = 0.020, p = 0.004 respectively), TNM stage (p < 0.001 for both), poor survival (p < 0.001 for both), and with increased rate of recurrence (p = 0.020, p = 0.005 respectively).ConclusionCD44 and cyclin D1 were associated with poor prognosis in gastric cancer, and so, they comprise an attractive target for anticancer drug development.

The Prognostic Value of Cancer Stem Cell Markers (Notch1, ALDH1, and CD44) in Primary Colorectal Carcinoma

BackgroundCancer stem cells proved to have a vital role in cell migration, invasion, metastasis, and treatment resistance of colorectal cancer (CRC) that subsequently lead to poor clinical outcomes. These stem cells may be a novel therapeutic target for the management of CRC progression. Signals of the Notch-1 pathway are responsible for acquisition of stem cell characters. ALDH1 and CD44 are usually detected in stem cells in colorectal cancer.AimThe aims of this work are to evaluate the immunohistochemical expression of cancer stem cell markers ALDH1, Notch1, and CD44 in colorectal cancer and investigate their correlation with clinicopathological characters and patient survival.MethodsParaffin-embedded specimens of 70 patients with primary colorectal carcinoma were analyzed for Notch 1, ALDH1, and CD44 expressions by immunohistochemistry.ResultsNotch1 was mainly located in the cytoplasm of CRC tissues, rarely expressed in adjacent normal tissues. A highly statistically significant relationship was found between grading, lymphovascular invasion, the degree of lymphocytic infiltration, peritumoral budding, lymph node ratio, lymph node metastasis, and Notch1 expression (p < 0.001). There was a highly statistically significant relationship found between AJCC stage and Notch1 expression (p < 0.001). CD44 was mainly located in the cell membrane of CRC tissues. A highly statistically significant relationship was found between grading (p = 0.006), lymphovascular invasion, the degree of lymphocytic infiltration, peritumoral budding, lymph node metastasis, lymph node ratio, and CD44 expression (p < 0.001). There was a highly statistically significant relationship found between AJCC stage and CD44 expression (p < 0.001). ALDH1 was detected in the cytoplasm of the CRC tissue. A highly statistically significant relationship was found between grading, lymphovascular invasion, the degree of lymphocytic infiltration, peritumoral budding, lymph node metastasis, lymph node ratio, and ALDH1 expression (p < 0.001). There was a highly statistically significant relationship found between AJCC stage and ALDH1 expression (p < 0.001). There is a highly statistically significant direct correlation between Notch1, CD44 expression, and ALDH1 expression (p < 0.001).ConclusionsThere is a substantial correlation between Notch 1, ALDH1, and CD44 as cancer stem cell markers and lymph node metastasis, advanced stage and tumor recurrence in colorectal carcinoma.ConclusionExpression of stem cell markers ALDH1, Notch1, and CD44 correlates with poor prognosis in a CRC and represents an independent prognostic factor. They are associated with a feature of epithelial-mesenchymal transition evidenced by their association with high tumor burden.